A Randomized, Controlled, Phase 1/2 Trial of a Neisseria meningitidis Serogroup B Bivalent rLP2086 Vaccine in Healthy Children and Adolescents

Nissen, Michael D. MB BS*; Marshall, Helen S. MB BS, MD; Richmond, Peter C. MB BS‡§; Jiang, Qin MS; Harris, Shannon L. PhD; Jones, Thomas R. PhD; Jansen, Kathrin U. PhD; Perez, John L. MD

Pediatric Infectious Disease Journal:
doi: 10.1097/INF.0b013e31827b0d24
Vaccine Reports
Abstract

Background: Neisseria meningitidis serogroup B (MnB) is a significant cause of invasive meningococcal disease. Factor H binding protein (also known as LP2086) is a conserved outer membrane neisserial lipoprotein that has emerged as a strong candidate protein antigen for MnB vaccination. This study examined the safety, tolerability and immunogenicity of an initial formulation of a bivalent recombinant LP2086 (rLP2086) vaccine in healthy children and adolescents.

Methods: In this randomized, observer-blinded, parallel-group, multicenter trial conducted at 6 centers in Australia, 127 healthy participants aged 8–14 years were assigned to receive 20, 60 or 200 µg of the bivalent rLP2086 vaccine (n = 16, 45 and 45, respectively) or active control (Twinrix, n = 21) at 0, 1 and 6 months. Immunogenicity was assessed before the first dose and 1 month after doses 2 and 3. Local reactions, systemic events and other adverse events were recorded. The primary immunogenicity endpoint was the rate of seroconversion (≥4-fold rise in human complement serum bactericidal assay titer) against MnB strains expressing the homologous A05 or heterologous B02 LP2086 variants.

Results: The bivalent rLP2086 vaccine was generally well-tolerated, with mostly mild to moderate local reactions. The most common adverse events, headache and upper respiratory tract infection, occurred with similar frequency in each group. Post-dose 3 seroconversion rates against strains expressing B02 and A05 variants were 68.8–95.3% for rLP2086 recipients and 0% for Twinrix recipients.

Conclusions: The bivalent rLP2086 vaccine was well-tolerated and immunogenic in healthy children and adolescents, supporting further evaluation as a broadly protective MnB vaccine.

Author Information

From the *Queensland Paediatric Infectious Diseases Laboratory, Queensland Children’s Medical Research Institute, Royal Children’s Hospital and University of Queensland, Herston, Queensland; Vaccinology and Immunology Research Trials Unit, Women’s and Children’s Hospital and School of Paediatrics and Reproductive Health, University of Adelaide, North Adelaide, South Australia; University of Western Australia School of Paediatrics and Child Health; §Vaccine Trials Group, Telethon Institute for Child Health Research, Subiaco, Western Australia, Australia; and Pfizer Vaccine Research, Pearl River, NY.

Accepted for publication October 24, 2012.

This study was funded by Wyeth Pharmaceuticals (Pearl River, NY), which was acquired by Pfizer Inc (Pearl River, NY) in October 2009. MDN has received travel grants from Wyeth Australia to present independent research at international meetings, and currently and previously has been the principal investigator for clinical trials sponsored by Abbott (Abbott Park, IL), Baxter (Deerfield, IL), CSL Behring (King of Prussia, PA), GlaxoSmithKline (Rixensart, Belgium), MedImmune (Gaithersburg, MD), Merck (Whitehouse Station, NJ), Novartis, Sanofi-Pasteur (Swiftwater, PA), Wyeth and Pfizer. Pfizer provided travel costs for HSM to present the preliminary study findings at an international infectious diseases conference. HSM has been a member of a Wyeth scientific advisory board on pneumococcal disease and vaccines but has not received any honoraria or personal payment from Pfizer or Wyeth. Her institution has also received payment from Pfizer, GlaxoSmithKline and CSL Behring for travel support for presentation of scientific data at international meetings, as well as grant funding from GlaxoSmithKline, Novartis and Sanofi-Pasteur for investigator-led vaccine research. PCR has been a member of vaccine advisory boards for Wyeth and Baxter, has received funding for investigator-initiated research from GlaxoSmithKline Biologicals and Novartis and has received travel support from Pfizer and Baxter to present study data at international meetings. QJ, TRJ, SLH, KUJ and JLP are employees of Pfizer Inc. The authors have no other funding or conflicts of interest to disclose.

Address for correspondence: Michael D. Nissen, MB BS, Qpid Laboratory, Department of Cellular and Molecular Pathology, School of Medicine, Faculty of Health Sciences, University of Queensland, St. Lucia, Queensland 4072, Australia, E-mail: theniss@uq.edu.au.

© 2013 Lippincott Williams & Wilkins, Inc.